The objective of the project is to identify and characterize molecules that regulate cell proliferation in normal and neoplastic cells and to understand the mechanism of action of these molecules. We also intend to develop tissue-specific reagents by isolating monoclonal antibodies to intermediate filament proteins. We have found that many malignant cells in culture do not require platelet-derived growth factor (PDGF) or epidermal growth factor (EGF) for growth. The neoplastic cells do not possess cell surface PDGF receptors, but do have EGF-specific receptors. In addition, conditioned medium from the tumor cells contains an activity that competes with 125I-labeled PDGF for binding to the PDGF receptor. We are currently characterizing this activity. Five different anti-intermediate filament protein antibodies have been isolated. An antivimentin antibody only stains mesenchymal tissue. Three different anticytokeratin antibodies recognize different classes of epithelial cells. One stains only the suprabasal portion of squamous epithelium, another stains the full thickness of squamous epithelium and ductular epithelium and a third stains all nonsquamous epithelium but fails to stain squamous epithelium. We are using these antibodies as diagnostic reagents to identify the cellular origin of poorly differentiated neoplasms.